Lymphoma – personalised medicine

Personalised medicine – identifying
the best treatment for the individual patient – is not new, but its role in healthcare
is rapidly increasing.

The
aim of personalised medicine is to optimise outcomes by integrating information
on tumour biology (obtained through genomics technologies) with clinical
information, and tailoring therapy.

Better
knowledge of a cancer’s molecular biology means clinicians can increasingly
tell the many biologic differences between individual patients’ cancers, and a
greater ability to measure biologic characteristics helps point to the use of a
specific, or targeted drug.

In
lymphoma, many treatment options available, and knowing more about the
different subtypes enables the most effective treatment to be selected for each
patient.

Personalised medicine and lymphoma

Clinical
practice for lymphoma has relied on treatment algorithms (a best practice approach to medical treatment) to provide similar
treatments to large subgroups of patients. Now, clinicians realise unique
biologic differences exist among the different subtypes of lymphomas and
between individuals with the same subtype.

In
diffuse large B-cell lymphoma (DLBCL) – the most common form of aggressive
non-Hodgkin lymphoma – gene expression profiling has identified two main
biologic subtypes – activated B-cell-like (ABC) and germinal centre B-cell-like
(GCB), and 85% of patients with DLBCL have either ABC or GCB subtypes.

Most
people with DLBCL are treated in a similar way, regardless of subtype, but this
information will become more relevant soon as there are drugs in development
that are expected to benefit one subtype or the other, such as ibrutinib, a
selective, irreversible inhibitor of Bruton’s tyrosine kinase that is typically
expressed in the ABC subtype.

Another
example is double hit lymphoma. These patients have two genetic abnormalities and it’s
important that they are appropriately identified as they typically do not do
well with the present standard treatment for DLBCL.

Is gene expression profiling for everyone?

Most
treatment decisions in lymphoma are still not based on a patient’s genetic
profile, and gene expression profiling isn’t routine care for all patients.
There are some simple immunohistochemistry tests that can help identify people
with ABC or GCB DLBCL, but these techniques are not perfect and there is debate
about whether these tests should be done.

As
more is learned about the biology of the different lymphomas and as more
selective treatments are developed, tools to measure genetic differences will
need to become routinely available.

Benefits of personalised medicine

Being
smarter in choosing the best drug for an individual patient means providing the
optimal treatment, with the highest chance of helping the patient and sparing
them the unnecessary toxicity of a drug that is not likely to work. Newer, more
targeted therapies are likely to be expensive, so it is imperative that they
are given to patients who will benefit.

Changes in drug
development

Whereas
chemotherapy has a broad mechanism of action, most drugs in development are
‘targeted therapies’ with a known specific mode of action that is efficacious
for certain cancers. And, as the design of most drugs in development is based
on genetic differences and abnormalities, clinical trials have biologic
questions built into them to test whether patients have those biologic
features.

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